Association of COLIA1 Sp1 Alleles with Defective Bone Nodule Formation In Vitro and Abnormal Bone Mineralization In Vivo (original) (raw)

Abstract

Previous work identified a G/T polymorphism affecting a Sp1 binding site in a regulatory region of the COLIA1 gene that predisposes to osteoporotic fractures by affecting bone strength through mechanisms that are partly independent of differences in bone mineral density (BMD). To clarify the mechanisms by which COLIA1 Sp1 alleles influence bone strength we used quantitative backscattered electron imaging (qBEI) to characterize bone mineralization in biopsy samples from subjects of different COLIA1 genotype and studied the ability of osteoblast-like cells cultured from subjects of different genotypes to form mineralized bone nodules. The qBEI analysis showed a significant (P = 0.014) reduction in mineralization in bone biopsies from G/T heterozygotes (n = 6) compared with G/G homozygotes (n = 7) and a significant increase in heterogeneity of mineralization (P = 0.017). The in vitro studies showed that osteoblasts derived from G/T heterozygotes (n = 5) were significantly less able to produce mineralized bone nodules than G/G homozygotes (n = 10) at all time-points examined (P < 0.0001). We conclude that carriage of the COLIA1 Sp1 “T” allele is associated with an impaired ability of osteoblast-like cells to form mineralized bone nodules in vitro and with abnormalities of bone mineralization in vivo. This suggests that the increased bone fragility in carriers of the COLIA1 Sp1 allele may result in part from defects in bone mineralization.

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Authors and Affiliations

  1. Department of Medicine and Therapeutics, University of Aberdeen Medical School, Aberdeen, AB25 2ZD, UK
    T. L. Stewart & R. Aspden
  2. Ludwig Boltzmann Institute of Osteology, 4th Med. Dept., Hanusch Hospital & UKH Meidling, Vienna, Austria
    P. Roschger, B. M. Misof & K. Klaushofer
  3. Max-Planck-Institute of Colloids and Interfaces, Department of Biomaterials, Potsdam, 14424, Germany
    P. Fratzl
  4. Rheumatic Diseases Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH42XU, UK
    V. Mann & S. H. Ralston

Authors

  1. T. L. Stewart
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  2. P. Roschger
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  3. B. M. Misof
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  4. V. Mann
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  5. P. Fratzl
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  6. K. Klaushofer
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  7. R. Aspden
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  8. S. H. Ralston
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Corresponding author

Correspondence toS. H. Ralston.

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T.L.S. and P.R. contributed equally.

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Stewart, T.L., Roschger, P., Misof, B.M. et al. Association of COLIA1 Sp1 Alleles with Defective Bone Nodule Formation In Vitro and Abnormal Bone Mineralization In Vivo .Calcif Tissue Int 77, 113–118 (2005). https://doi.org/10.1007/s00223-004-0188-8

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